Dibenzoylmethane, hydroxydibenzoylmethane and hydroxymethyldibenzoylmethane inhibit phorbol-12-myristate 13-acetate‑induced breast carcinoma cell invasion

Liao,Ya‑Fan; Tzeng,Yew‑Min; Hung,Hui‑Chih; Liu,Guang‑Yaw

doi:10.3892/mmr.2015.3304

Dibenzoylmethane, hydroxydibenzoylmethane and hydroxymethyldibenzoylmethane inhibit phorbol-12-myristate 13-acetate‑induced breast carcinoma cell invasion

Authors:
- Ya‑Fan Liao
- Yew‑Min Tzeng
- Hui‑Chih Hung
- Guang‑Yaw Liu
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Affiliations: Department of Applied Chemistry, Chaoyang University of Technology, Taichung 41349, Taiwan, R.O.C., Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan, R.O.C., Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
Published online on: February 4, 2015 https://doi.org/10.3892/mmr.2015.3304
Pages: 4597-4604

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Abstract

Dibenzoylmethane (DB), a minor constituent of the root extract of licorice, belongs to the flavonoid family. Hydroxydibenzoylmethane (HDB) and hydroxymethyldibenzoylmethane (HMDB) have an identical structure to DB, but also possess a hydroxyl group and a hydroxyl and methyl group bonded to aromatic rings, respectively. They inhibit cellular proliferation and induce apoptosis in a variety of types of cancer cell, however, the antimetastatic effects of DB, HDB and HMDB on human breast carcinoma cells remain to be elucidated. The present study aimed to clarify the molecular mechanisms underlying the effects of DB and its analogues on phorbol‑12‑myristate 13‑acetate (PMA)‑induced MCF‑7 cell metastasis. The results revealed that DB, HDB and HMDB inhibited cell migration and invasion. In addition, PMA‑mediated MCF‑7 cell invasion was inhibited by DB, HDB and HMDB by inhibiting the expression of matrix metalloproteinase (MMP)‑9. Rottlerin, a protein kinase C (PKC)δ inhibitor and LY294002, a phosphatidylinositide 3‑kinase (PI3K) inhibitor, reduced the PMA‑mediated expression of MMP‑9 and cell invasion. Furthermore, DB, HDB and HMDB prevented the activation of PKCδ and PI3K by inhibiting their phosphorylation. The present study was the first, to the best of our knowledge, to demonstrate the antimetastatic potential of DB, HDB and HDMB, which decreased cancer cell invasion through the PI3K/PKCδ‑mediated MMP‑9 pathway.

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1	Weigelt B, Peterse JL and van’t Veer LJ: Breast cancer metastasis: markers and models. Nat Rev Cancer. 5:591–602. 2005. View Article : Google Scholar : PubMed/NCBI
2	Scully OJ, Bay BH, Yip G and Yu Y: Breast cancer metastasis. Cancer Genomics Proteomics. 9:311–320. 2012.PubMed/NCBI
3	Stetler-Stevenson WG, Aznavoorian S and Liotta LA: Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol. 9:541–573. 1993. View Article : Google Scholar : PubMed/NCBI
4	Vihinen P and Kahari VM: Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer. 99:157–166. 2002. View Article : Google Scholar : PubMed/NCBI
5	Kondraganti S, Mohanam S, Chintala SK, et al: Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. Cancer Res. 60:6851–6855. 2000.
6	Lakka SS, Gondi CS, Yanamandra N, et al: Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene. 23:4681–4689. 2004. View Article : Google Scholar : PubMed/NCBI
7	Itoh T, Tanioka M, Matsuda H, et al: Experimental metastasis is suppressed in MMP-9-deficient mice. Clin Exp Metastasis. 17:177–181. 1999. View Article : Google Scholar : PubMed/NCBI
8	Ji MK, Shi Y, Xu JW, et al: Recombinant snake venom metalloproteinase inhibitor BJ46A inhibits invasion and metastasis of B16F10 and MHCC97H cells through reductions of matrix metalloproteinases 2 and 9 activities. Anticancer Drugs. 24:461–472. 2013. View Article : Google Scholar : PubMed/NCBI
9	Shishu, Singla AK and Kaur IP: Inhibitory effect of dibenzoylmethane on mutagenicity of food-derived heterocyclic amine mutagens. Phytomedicine. 10:575–582. 2003. View Article : Google Scholar : PubMed/NCBI
10	Lin CC, Lu YP, Lou YR, et al: Inhibition by dietary dibenzoylmethane of mammary gland proliferation, formation of DMBA-DNA adducts in mammary glands, and mammary tumorigenesis in Sencar mice. Cancer Lett. 168:125–132. 2001. View Article : Google Scholar : PubMed/NCBI
11	Singletary K and MacDonald C: Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells bydibenzoylmethane and sulforaphane. Cancer Lett. 155:47–54. 2000. View Article : Google Scholar : PubMed/NCBI
12	Cheung KL, Khor TO, Huang MT and Kong AN: Differential in vivo mechanism of chemoprevention of tumor formation in azoxymethane/dextran sodium sulfate mice by PEITC and DBM. Carcinogenesis. 31:880–885. 2010. View Article : Google Scholar :
13	Singletary K, MacDonald C, Iovinelli M, Fisher C and Wallig M: Effect of the beta-diketones diferuloylmethane (curcumin) and dibenzoylmethane on rat mammary DNA adducts and tumors induced by 7,12-dimethylbenz[a]anthracene. Carcinogenesis. 19:1039–1043. 1998. View Article : Google Scholar : PubMed/NCBI
14	Jackson KM, DeLeon M, Verret CR and Harris WB: Dibenzoylmethane induces cell cycle deregulation in human prostate cancer cells. Cancer Lett. 178:161–165. 2002. View Article : Google Scholar : PubMed/NCBI
15	Pan MH, Sin YH, Lai CS, et al: Induction of apoptosis by 1-(2-hydr oxy-5-methylphenyl)-3-phenyl-1,3-propanedione through reactive oxygen species production, GADD153 expression, and caspases activation in human epidermoid carcinoma cells. J Agric Food Chem. 53:9039–9049. 2005. View Article : Google Scholar : PubMed/NCBI
16	Weng CJ, Yang YT, Ho CT and Yen GC: Mechanisms of apoptotic effects induced by resveratrol, dibenzoylmethane, and their analogues on human lung carcinoma cells. J Agric Food Chem. 57:5235–5243. 2009. View Article : Google Scholar : PubMed/NCBI
17	Wu CL, Liao YF, Hung YC, Lu KH, Hung HC and Liu GY: Ornithine decarboxylase prevents dibenzoylmethane-induced apoptosis through repressing reactive oxygen species generation. J Biochem Mol Toxicol. 25:312–319. 2011. View Article : Google Scholar : PubMed/NCBI
18	Pan MH, Huang MC, Wang YJ, Lin JK and Lin CH: Induction of apoptosis by hydroxydibenzoylmethane through coordinative modulation of cyclin D3, Bcl-X(L), and Bax, release of cytochrome c, and sequential activation of caspases in human colorectal carcinoma cells. J Agric Food Chem. 51:3977–3984. 2003. View Article : Google Scholar : PubMed/NCBI
19	Liao YF, Rao YK and Tzeng YM: Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-kappaB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells. Food Chem Toxicol. 50:2930–2936. 2012. View Article : Google Scholar : PubMed/NCBI
20	Duffy MJ, Maguire TM, Hill A, McDermott E and O’Higgins N: Metalloproteinases: Role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res. 2:252–257. 2000. View Article : Google Scholar
21	Park SK, Hwang YS, Park KK, Park HJ, Seo JY and Chung WY: Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells. Carcinogenesis. 30:1225–1233. 2009. View Article : Google Scholar : PubMed/NCBI
22	Yu HS, Lin TH and Tang CH: Bradykinin enhances cell migration in human prostate cancer cells through B2 receptor/PKCdelta/c-Src dependent signaling pathway. Prostate. 73:89–100. 2013. View Article : Google Scholar
23	Pockaj BA, Wasif N, Dueck AC, et al: Metastasectomy and surgical resection of the primary tumor in patients with stage IV breast cancer: time for a second look? Ann Surg Oncol. 17:2419–2426. 2010. View Article : Google Scholar : PubMed/NCBI
24	Johnson KA and Brown PH: Drug development for cancer chemoprevention: focus on molecular targets. Semin Oncol. 37:345–358. 2010. View Article : Google Scholar : PubMed/NCBI
25	Weng CJ and Yen GC: Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treat Rev. 38:76–87. 2012. View Article : Google Scholar
26	Kandaswami C, Lee LT, Lee PP, et al: The antitumor activities of flavonoids. In Vivo. 19:895–909. 2005.PubMed/NCBI
27	Nogueira MA, Magalhaes EG, Magalhaes AF, et al: A novel sunscreen agent having antimelanoma activity. Farmaco. 58:1163–1169. 2003. View Article : Google Scholar : PubMed/NCBI
28	Dinkova-Kostova AT and Talalay P: Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. Carcinogenesis. 20:911–914. 1999. View Article : Google Scholar : PubMed/NCBI
29	Brummer O, Athar S, Riethdorf L, Loning T and Herbst H: Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch. 435:566–573. 1999. View Article : Google Scholar
30	Mishra A, Paul S and Swarnakar S: Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice. Biochimie. 93:854–866. 2011. View Article : Google Scholar : PubMed/NCBI
31	Huang MT, Lou YR, Xie JG, et al: Effect of dietary curcumin and dibenzoylmethane on formation of 7,12-dimethylbenz[a] anthracene-induced mammary tumors and lymphomas/leukemias in Sencar mice. Carcinogenesis. 19:1697–1700. 1998. View Article : Google Scholar : PubMed/NCBI
32	Lin CW, Hou WC, Shen SC, et al: Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis. 29:1807–1815. 2008. View Article : Google Scholar : PubMed/NCBI
33	Sim GS, Lee BC, Cho HS, et al: Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast. Arch Pharm Res. 30:290–298. 2007. View Article : Google Scholar : PubMed/NCBI
34	Liu WS and Heckman CA: The sevenfold way of PKC regulation. Cell Signal. 10:529–542. 1998. View Article : Google Scholar : PubMed/NCBI
35	Matsuoka H, Tsubaki M, Yamazoe Y, et al: Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways. Exp Cell Res. 315:2022–2032. 2009. View Article : Google Scholar : PubMed/NCBI
36	Hussaini IM, Trotter C, Zhao Y, et al: Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line. Am J Pathol. 170:356–365. 2007. View Article : Google Scholar : PubMed/NCBI
37	Woo JH, Lim JH, Kim YH, et al: Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene. 23:1845–1853. 2004. View Article : Google Scholar
38	Vuong H, Patterson T, Shapiro P, et al: Phorbol ester-induced expression of airway squamous cell differentiation marker, SPRR1B, is regulated by protein kinase Cdelta/Ras/MEKK1/MKK1-dependent/AP-1 signal transduction pathway. J Biol Chem. 275:32250–32259. 2000. View Article : Google Scholar : PubMed/NCBI
39	Chang JT, Lu YC, Chen YJ, et al: hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells. Br J Cancer. 94:870–878. 2006. View Article : Google Scholar : PubMed/NCBI
40	Lin CC, Tsai YL, Huang MT, et al: Inhibition of estradiol-induced mammary proliferation by dibenzoylmethane through the E2-ER-ERE-dependent pathway. Carcinogenesis. 27:131–136. 2006. View Article : Google Scholar
41	Lee KW, Kim MS, Kang NJ, et al: H-Ras selectively up-regulates MMP-9 and COX-2 through activation of ERK1/2 and NF-kappaB: an implication for invasive phenotype in rat liver epithelial cells. Int J Cancer. 119:1767–1775. 2006. View Article : Google Scholar : PubMed/NCBI
42	George J, Banik NL and Ray SK: Knockdown of hTERT and concurrent treatment with interferon-gamma inhibited proliferation and invasion of human glioblastoma cell lines. Int J Biochem Cell Biol. 42:1164–1173. 2010. View Article : Google Scholar : PubMed/NCBI
43	Park EJ, Lim JH, Nam SI, Park JW and Kwon TK: Rottlerin induces heme oxygenase-1 (HO-1) up-regulation through reactive oxygen species (ROS) dependent and PKC delta-independent pathway in human colon cancer HT29 cells. Biochimie. 92:110–115. 2010. View Article : Google Scholar
44	Pan YC, Li CF, Ko CY, et al: CEBPD reverses RB/E2F1-mediated gene repression and participates in HMDB-induced apoptosis of cancer cells. Clin Cancer Res. 16:5770–5780. 2010. View Article : Google Scholar : PubMed/NCBI
45	Lee KH and Kim JR: Kiss-1 suppresses MMP-9 expression by activating p38 MAP kinase in human stomach cancer. Oncol Res. 18:107–116. 2009. View Article : Google Scholar
46	Adamo B, Deal AM, Burrows E, et al: Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Res. 13:R1252011. View Article : Google Scholar : PubMed/NCBI
47	Cuevas BD, Lu Y, Mao M, et al: Tyrosine phosphorylation of p85 relieves its inhibitory activity on phosphatidylinositol 3-kinase. J Biol Chem. 276:27455–27461. 2001. View Article : Google Scholar : PubMed/NCBI
48	Liu C, Su T, Li F, et al: PI3K/Akt signaling transduction pathway is involved in rat vascular smooth muscle cell proliferation induced by apelin-13. Acta Biochim Biophys Sin (Shanghai). 42:396–402. 2010. View Article : Google Scholar